1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamino]ethane (Dofetilide) is prepared by sulfonylation of 1-(4-aminophenoxy)-2-[N-(4-aminophenethyl)-N-methylamino]ethane, the compound of formula II.

Preparation of 1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamino]ethane (Dofetilide) was first described in EP0245997 through a reaction of 1-(4-aminophenoxy)-2-[N-(4-aminophenethyl)-N-methylamino]ethane with the anhydride of methanesulfonic acid (methanesulfonic anhydride). The starting compound reacts with methanesulfonic anhydride in a dichloromethane environment without the use of a base. Disadvantages of this procedure include the price of methanesulfonic anhydride and at the same time an inconvenient atom economy of the process. The same procedure was subsequently described in the reference literature (Cross P. E., Arrowsmith J. E., Thomas G. N., Gwilt M., Burges R. A., Higgins A. J., J. Med. Chem., 1990, 33, 1151-1155). Preparation of 1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamino]ethane (Dofetilide) was further described in U.S. Pat. No. 6,124,363, where methanesulfonyl chloride is used as the sulfonylation agent in the presence of triethylamine. Methanesulfonyl chloride is a very reactive agent and under the described conditions, undesired methanesulfonimides are produced, which must be hydrolyzed with use of sodium hydroxide during the processing of the reaction mixture. Subsequently, the product is isolated by adjustment of pH of the mixture and filtration. The product is separated in the form of a fine precipitate, the filtration of which is time consuming. In addition, the product may be polluted by inorganic salts. 1-(4-Methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamino]ethane (Dofetilide) has also been synthesized by arylation of methanesulfonamide catalyzed by palladium (Rosen B. R., Ruble J. C., Beauchamp T. J., Navarro A., Org. Lett., 2011, 13, 2564-2567); this method has drawbacks in the price of the used catalyst and ligand and contamination of the product by palladium.
The said disadvantages are eliminated by the method according to the invention.